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Benchmarking of alignment-free sequence comparison methods
Background
Alignment-free (AF) sequence comparison is attracting persistent interest driven by data-intensive applications. Hence, many AF procedures have been proposed in recent years, but a lack of a clearly defined benchmarking consensus hampers their performance assessment.
Results
Here, we present a community resource (
http://afproject.org
) to establish standards for comparing alignment-free approaches across different areas of sequence-based research. We characterize 74 AF methods available in 24 software tools for five research applications, namely, protein sequence classification, gene tree inference, regulatory element detection, genome-based phylogenetic inference, and reconstruction of species trees under horizontal gene transfer and recombination events.
Conclusion
The interactive web service allows researchers to explore the performance of alignment-free tools relevant to their data types and analytical goals. It also allows method developers to assess their own algorithms and compare them with current state-of-the-art tools, accelerating the development of new, more accurate AF solutions.
Journal Article
Rabbits, rabbits everywhere : a Fibonacci tale
Rapidly multiplying rabbits are taking over the village of Chee, and soon there are so many that even the Pied Piper cannot get rid of them, but a girl named Amanda discovers a pattern that leads to a way to make the rabbits leave.
Book
Pooling designs and nonadaptive group testing
Pooling designs have been widely used in various aspects of DNA sequencing. In biological applications, the well-studied mathematical problem called “group testing” shifts its focus to nonadaptive algorithms while the focus of traditional group testing is on sequential algorithms. Biological applications also bring forth new models not previously considered, such as the error-tolerant model, the complex model, and the inhibitor model. This book is the first attempt to collect all the significant research on pooling designs in one convenient place.
eBook
Wild Fibonacci : nature's secret code revealed
Discover the fibonacci sequence as it appears in nature, from the curves of a sundial shell, to a parrot's beak, a hawk's talon, a ram's horn, and even human teeth!
Book
Long-read sequencing for rare human genetic diseases
During the past decade, the search for pathogenic mutations in rare human genetic diseases has involved huge efforts to sequence coding regions, or the entire genome, using massively parallel short-read sequencers. However, the approximate current diagnostic rate is <50% using these approaches, and there remain many rare genetic diseases with unknown cause. There may be many reasons for this, but one plausible explanation is that the responsible mutations are in regions of the genome that are difficult to sequence using conventional technologies (e.g., tandem-repeat expansion or complex chromosomal structural aberrations). Despite the drawbacks of high cost and a shortage of standard analytical methods, several studies have analyzed pathogenic changes in the genome using long-read sequencers. The results of these studies provide hope that further application of long-read sequencers to identify the causative mutations in unsolved genetic diseases may expand our understanding of the human genome and diseases. Such approaches may also be applied to molecular diagnosis and therapeutic strategies for patients with genetic diseases in the future.
Journal Article
Horrible Harry cracks the code
Horrible Harry must defend his reputation as a detective by cracking the secret code of Mrs. Funderburke's lunch prizes.
Book
Köthe-Töeplitz duals of vector valued sequence spaces defined by φ-function
Let f be any φ-function and E be a complete normed space. In this paper, we constuct the new classes (W∞)f(E), (W)f(E) and (W0)f(E) of vector valued sequences using φ-function f and investigate the Köthe-Töeplitz duals of these classes.
Journal Article
A Universal Probe Set for Targeted Sequencing of 353 Nuclear Genes from Any Flowering Plant Designed Using k-Medoids Clustering
Sequencing of target-enriched libraries is an efficient and cost-effective method for obtaining DNA sequence data from hundreds of nuclear loci for phylogeny reconstruction. Much of the cost of developing targeted sequencing approaches is associated with the generation of preliminary data needed for the identification of orthologous loci for probe design. In plants, identifying orthologous loci has proven difficult due to a large number of whole-genome duplication events, especially in the angiosperms (flowering plants). We used multiple sequence alignments from over 600 angiosperms for 353 putatively single-copy protein-coding genes identified by the One Thousand Plant Transcriptomes Initiative to design a set of targeted sequencing probes for phylogenetic studies of any angiosperm group. To maximize the phylogenetic potential of the probes, while minimizing the cost of production, we introduce a k-medoids clustering approach to identify the minimum number of sequences necessary to represent each coding sequence in the final probe set. Using this method, 5–15 representative sequences were selected per orthologous locus, representing the sequence diversity of angiosperms more efficiently than if probes were designed using available sequenced genomes alone. To test our approximately 80,000 probes, we hybridized libraries from 42 species spanning all higher-order groups of angiosperms, with a focus on taxa not present in the sequence alignments used to design the probes. Out of a possible 353 coding sequences, we recovered an average of 283 per species and at least 100 in all species. Differences among taxa in sequence recovery could not be explained by relatedness to the representative taxa selected for probe design, suggesting that there is no phylogenetic bias in the probe set. Our probe set, which targeted 260 kbp of coding sequence, achieved a median recovery of 137 kbp per taxon in coding regions, a maximum recovery of 250 kbp, and an additional median of 212 kbp per taxon in flanking non-coding regions across all species. These results suggest that the Angiosperms353 probe set described here is effective for any group of flowering plants and would be useful for phylogenetic studies from the species level to higher-order groups, including the entire angiosperm clade itself.
Journal Article
Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal Omega
Multiple sequence alignments are fundamental to many sequence analysis methods. Most alignments are computed using the progressive alignment heuristic. These methods are starting to become a bottleneck in some analysis pipelines when faced with data sets of the size of many thousands of sequences. Some methods allow computation of larger data sets while sacrificing quality, and others produce high‐quality alignments, but scale badly with the number of sequences. In this paper, we describe a new program called Clustal Omega, which can align virtually any number of protein sequences quickly and that delivers accurate alignments. The accuracy of the package on smaller test cases is similar to that of the high‐quality aligners. On larger data sets, Clustal Omega outperforms other packages in terms of execution time and quality. Clustal Omega also has powerful features for adding sequences to and exploiting information in existing alignments, making use of the vast amount of precomputed information in public databases like Pfam.
Multiple sequence alignments are fundamental to many sequence analysis methods. The new program Clustal Omega can align virtually any number of protein sequences quickly and has powerful features for adding sequences to existing precomputed alignments.
Journal Article